tbuckley/cabot-search huggingface dataset:
Diverticular disease and cancer risk: More than a gut feeling
Authors: Veronika Fedirko, Scott Kopetz, Carrie R Daniel
Journal: JNCI Journal of the National Cancer Institute (2022)

Diverticular disease of the colon is among the most common gastrointestinal disorders in Western countries.It is a clinically significant and symptomatic diverticulosis, which is defined by the presence of a pouch-like protrusion of the colonic wall known as diverticula.Diverticular disease could present itself as diverticular bleeding, perforation, colitis, inflammation, or abdominal pain and, generally, is regarded as a heterogenous disease.Given its relatively high prevalence (more than 50% by age 60 years by some estimates) (1) and need for a medical intervention, it is a substantial contributor to health-care costs and hospital admissions.The study by Ma et al.(2) published in the current edition of the Journal provides new information about cancer risk among patients with diverticular disease.In the Swedish population-based
Effectiveness of Antipsychotic Use for Reducing Risk of Work Disability: Results From a Within-Subject Analysis of a Swedish National Cohort of 21,551 Patients With First-Episode Nonaffective Psychosis
Authors: Marco Solmi, Heidi Taipale, Minna Holm, Antti Tanskanen, Ellenor Mittendorfer-Rutz, Christoph U. Correll, Jari Tiihonen
Journal: American Journal of Psychiatry (2022)

The authors sought to determine whether antipsychotic use, compared with nonuse, is associated with lower work disability in first-episode nonaffective psychosis, and if so, for how long.A within-subject design was used to study the risk of sickness absence or disability pension during antipsychotic use compared with nonuse during a maximum of 11 years of follow-up (2006-2016) in a Swedish nationwide cohort of patients with first-episode nonaffective psychosis (N=21,551; age range, 16-45 years). The within-subject analyses were conducted with stratified Cox regression models, adjusted for time-varying factors, using each individual as her or his own control to eliminate selection bias. The primary outcome was work disability (sickness absence or disability pension).Overall, 45.9% of first-episode patients had work disability during the median length of follow-up of 4.8 years. The risk of work disability was lower during use compared with nonuse of any antipsychotic (adjusted hazard ratio [aHR]=0.65, 95% CI=0.59-0.72). The lowest adjusted hazard ratios emerged for long-acting injectable antipsychotics (aHR=0.46, 95% CI=0.34-0.62), oral aripiprazole (aHR=0.68, 95% CI=0.56-0.82), and oral olanzapine (aHR=0.68, 95% CI=0.59-0.78). Long-acting injectables were associated with lower risk than olanzapine, the most commonly used oral antipsychotic (aHR=0.68, 95% CI=0.50-0.94). Adjusted hazard ratios were similar during the periods of <2 years, 2-5 years, and >5 years since diagnosis.Among individuals with first-episode nonaffective psychosis, antipsychotic treatment (with long-acting injectables in particular) was associated with about 30%-50% lower risk of work disability compared with nonuse of antipsychotics in the same individuals, which held true beyond 5 years after first diagnosis. These findings are informative regarding the important topic of early discontinuation of antipsychotic treatment after a first episode of nonaffective psychosis, but they need replication.
Endothelial RBPJ Is Essential for the Education of Tumor-Associated Macrophages
Authors: Elisenda Alsina-Sanchis, Ronja Mülfarth, Iris Moll, Sarah Böhn, Lena Wiedmann, Lorea Jordana-Urriza, Tara Ziegelbauer, Eleni Zimmer, Jacqueline Taylor, Francesca De Angelis Rigotti, Adrian Stögbauer, Benedetto Daniele Giaimo, Adelheid Cerwenka, Tilman Borggrefe, Andreas Fischer, Juan Rodriguez-Vita
Journal: Cancer Research (2022)

Abstract Epithelial ovarian cancer (EOC) is one of the most lethal gynecologic cancers worldwide. EOC cells educate tumor-associated macrophages (TAM) through CD44-mediated cholesterol depletion to generate an immunosuppressive tumor microenvironment (TME). In addition, tumor cells frequently activate Notch1 receptors on endothelial cells (EC) to facilitate metastasis. However, further work is required to establish whether the endothelium also influences the education of recruited monocytes. Here, we report that canonical Notch signaling through RBPJ in ECs is an important player in the education of TAMs and EOC progression. Deletion of Rbpj in the endothelium of adult mice reduced infiltration of monocyte-derived macrophages into the TME of EOC and prevented the acquisition of a typical TAM gene signature; this was associated with stronger cytotoxic activity of T cells and decreased tumor burden. Mechanistically, CXCL2 was identified as a novel Notch/RBPJ target gene that regulated the expression of CD44 on monocytes and subsequent cholesterol depletion of TAMs. Bioinformatic analysis of ovarian cancer patient data showed that increased CXCL2 expression is accompanied by higher expression of CD44 and TAM education. Together, these findings indicate that EOC cells induce the tumor endothelium to secrete CXCL2 to establish an immunosuppressive microenvironment. Significance: Endothelial Notch signaling favors immunosuppression by increasing CXCL2 secretion to stimulate CD44 expression in macrophages, facilitating their education by tumor cells.
Sussing Out Adjuvant ICI's Utility in RCC
Journal: Cancer Discovery (2022)

Whether adjuvant immune checkpoint inhibition cuts recurrence risk in patients with localized renal cell carcinoma, as the phase III KEYNOTE-564 study showed, is unclear. Three other adjuvant trials-CheckMate-914, IMmotion010, and PROSPER-recently reported no disease-free survival improvement, casting some doubt on the utility of this approach.
Mode and Tempo of 3D Genome Evolution in <i>Drosophila</i>
Authors: Nicole S Torosin, Tirupathi Rao Golla, Matthew A Lawlor, Weihuan Cao, Christopher E Ellison
Journal: Molecular Biology and Evolution (2022)

Abstract Topologically associating domains (TADs) are thought to play an important role in preventing gene misexpression by spatially constraining enhancer–promoter contacts. The deleterious nature of gene misexpression implies that TADs should, therefore, be conserved among related species. Several early studies comparing chromosome conformation between species reported high levels of TAD conservation; however, more recent studies have questioned these results. Furthermore, recent work suggests that TAD reorganization is not associated with extensive changes in gene expression. Here, we investigate the evolutionary conservation of TADs among 11 species of Drosophila. We use Hi-C data to identify TADs in each species and employ a comparative phylogenetic approach to derive empirical estimates of the rate of TAD evolution. Surprisingly, we find that TADs evolve rapidly. However, we also find that the rate of evolution depends on the chromatin state of the TAD, with TADs enriched for developmentally regulated chromatin evolving significantly slower than TADs enriched for broadly expressed, active chromatin. We also find that, after controlling for differences in chromatin state, highly conserved TADs do not exhibit higher levels of gene expression constraint. These results suggest that, in general, most TADs evolve rapidly and their divergence is not associated with widespread changes in gene expression. However, higher levels of evolutionary conservation and gene expression constraints in TADs enriched for developmentally regulated chromatin suggest that these TAD subtypes may be more important for regulating gene expression, likely due to the larger number of long-distance enhancer–promoter contacts associated with developmental genes.
Weighting by Gene Tree Uncertainty Improves Accuracy of Quartet-based Species Trees
Authors: Chao Zhang, Siavash Mirarab
Journal: Molecular Biology and Evolution (2022)

Abstract Phylogenomic analyses routinely estimate species trees using methods that account for gene tree discordance. However, the most scalable species tree inference methods, which summarize independently inferred gene trees to obtain a species tree, are sensitive to hard-to-avoid errors introduced in the gene tree estimation step. This dilemma has created much debate on the merits of concatenation versus summary methods and practical obstacles to using summary methods more widely and to the exclusion of concatenation. The most successful attempt at making summary methods resilient to noisy gene trees has been contracting low support branches from the gene trees. Unfortunately, this approach requires arbitrary thresholds and poses new challenges. Here, we introduce threshold-free weighting schemes for the quartet-based species tree inference, the metric used in the popular method ASTRAL. By reducing the impact of quartets with low support or long terminal branches (or both), weighting provides stronger theoretical guarantees and better empirical performance than the unweighted ASTRAL. Our simulations show that weighting improves accuracy across many conditions and reduces the gap with concatenation in conditions with low gene tree discordance and high noise. On empirical data, weighting improves congruence with concatenation and increases support. Together, our results show that weighting, enabled by a new optimization algorithm we introduce, improves the utility of summary methods and can reduce the incongruence often observed across analytical pipelines.
Antibiotics and Hepatic Artery Ligation in Germfree and Conventional Dogs
Authors: John N. Crook
Journal: JAMA (1970)

Anaerobic bacteria harbored in the liver of the dog have been shown to be the cause of death in this animal after hepatic artery ligation. The protective effect of antibiotics is well recognized. Forty-nine conventional and two germfree dogs were studied after hepatic artery ligation to evaluate this problem further. No conventional dogs survived without antibiotics. Antibiotics in large doses protected 81% of conventional dogs; 47% of dogs treated four days prior to surgery survived. The two germfree animals survived without antibiotics. This reaffirms the role of bacterial sepsis of the liver as the cause of death in the dog after hepatic artery ligation and emphasizes the small doses of antibiotics necessary for protection of conventional dogs and the survival of germfree dogs without antibiotics.
Cryosurgery for the Urethral Syndrome: Preliminary Communication
Authors: A C Parkes, P Boreham
Journal: Journal of the Royal Society of Medicine (1980)

A method has been devised for treating the urethral syndrome by cryosurgery using a special applicator. The results in the first 35 cases are presented and compared with a similar group of women treated by urethral dilatation. The cryosurgical method has proved to be successful and free of complications. The study is being continued.
Accumulation of organic anion in intracellular vesicles of cultured rat hepatocytes is mediated by the canalicular multispecific organic anion transporter
Authors: Ronald P. J. Oude Elferink, Conny T. M. Bakker, Han Roelofsen, Esther Middelkoop, Roelof Ottenhoff, Marc Heijn, Peter L. M. Jansen
Journal: Hepatology (1993)

Transport of organic anions within hepatocytes and the possible involvement of intracellular vesicles were studied with fluorescence microscopy. For this purpose monochlorobimane, a nonfluorescent hydrophobic compound that readily permeates into cells and is conjugated with glutathione to form the fluorescent glutathione bimane, was used. In the isolated perfused livers of normal rats, glutathione bimane is rapidly secreted into bile. In contrast, in our study of livers from mutant TR − rats, a 100-fold reduction in glutathione bimane secretion into bile occurred. Mutant TR − rats have an inherited defect in the canalicular multispecific organic anion transporter, which mediates the ATP-dependent secretion of a wide range of organic anions over the canalicular membrane into bile. When cultured Wistar and TR − hepatocytes were loaded with glutathione bimane, both cell types displayed a strong cytosolic fluorescence. Wistar cells completely lost this cytosolic fluorescence at incubation on monochlorobimane-free medium because of secretion of glutathione bimane. A clear punctate fluorescence remained, however, which was scattered through the cell with some perinuclear concentration. In some cells vesicular fluorescence was also concentrated around a canaliculus. In contrast, TR − cells lost their cytosolic fluorescence more slowly and completely lacked the vesicular fluorescence. Making cells selectively permeable with digitonin directly after loading them with glutathione bimane to remove cytosolic fluorescence again revealed the presence of fluorescent vesicles in Wistar cells and their absence in TR − cells. In Wistar cells vesicular fluorescence could be increased by preincubation with monensin or methylamine, compounds that have been shown to interfere with plasma membrane recycling. In conclusion, these results suggest that apart from secretion over the plasma membrane, the canalicular multispecific organic anion transporter may be involved in accumulation of organic anion in intracellular vesicles. It is hypothesized that this intracellular localization of the canalicular multispecific organic anion transporter is caused by recycling of the transporter between the plasma membrane and intracellular membranes. (Hepatology 1993;17:434-444.)
Editorial Freedom and Integrity
Authors: George D. Lundberg
Journal: JAMA (1988)

A medical editor has to be a keeper of the conscience of a profession; if he tries to live up to this ideal he will be always getting into trouble. Hugh Clegg, Quondam Editor,<i>British Medical Journal</i><sup>1</sup> At its annual meeting held at the National Library of Medicine in Bethesda, Md, on Sept 10 through 13, the International Committee of Medical Journal Editors (The Vancouver Group) unanimously approved a statement regarding editorial freedom. The members of the group who were present are Edward J. Huth, MD, editor,<i>Annals of Internal Medicine;</i>Kathleen King, MRCPath, editor, the<i>Medical Journal of Australia;</i>Stephen P. Lock, MD, editor, the<i>British Medical Journal;</i>George D. Lundberg, MD, editor,<i>The Journal of the American Medical Association;</i>Magne Nylenna, MD, editor,<i>Tidsskrift for Den Norkse Laegeforening;</i>Arnold S. Relman, MD, editor in chief,<i>New England Journal of Medicine;</i>Dr Povl Riis, editor in chief, Danish
A Reference Handbook of the Medical Sciences, Embracing the Entire Range of Scientific and Practical Medicine and Allied Science.
Journal: JAMA (1902)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Gonorrhea Detection by Urine Sediment Culture
Authors: George Moore
Journal: JAMA (1973)

From 392 men examined at a venereal disease clinic, 238 cases of gonorrhea (60.7%) were identified by culturing gonococci, using traditional loop and swab techniques of gathering urethral specimens and a new procedure employing the sediment from a patient's voided urine as a specimen source. In the patients proved to be infected as shown by the more difficult loop and swab cultural techniques, only 5.9% of the urine sediment cultures were negative. Of the cases positive by culture, 18.4% were clinically asymptomatic, a fifth of these being contacts of patients with known gonorrhea. The urine sediment culture method is a valuable new tool in screening for gonorrhea.
Highlights of This Issue
Journal: Clinical Cancer Research (2011)

Merkel cell carcinoma (MCC) is an aggressive skin cancer with limited treatment options for progressive disease.The Merkel cell polyomavirus (MCPyV) is integrated into most MCC tumors, and it encodes oncoproteins required for ongoing tumor growth.Iyer and colleagues identified MCPyV-specific CD8 and CD4 T-cell responses from MCC tumors and blood.The 26 novel MCPyV epitopes identified in this report will facilitate isolation of tumor-specific T lymphocytes, further characterization of immune evasion mechanisms used by this cancer, and development of MCPyV-specific immunotherapy for Merkel cell carcinoma.
Blood Flow In Normal Tissues and Tumors During Hyperthermia&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN2"&gt;3&lt;/xref&gt;
Authors: Chang W. Song, Juong G. Rhee, Seymour H. Levitt
Journal: JNCI Journal of the National Cancer Institute (1980)

The effect of hyperthermia on the blood flow was studied in skin, muscle, and Walker 256 carcinoma implanted in the legs of SD rats. The radioactive microsphere method was used to measure the blood flow. Hyperthermia for 1 hour with water at 43° C increased the blood flow in skin and muscle by about threefold to fourfold. On the contrary, hyperthermia had no appreciable effect on the blood flow in tumors. Consequently, during hyperthermia blood flow in the skin and muscle surrounding the tumors was greater than that in tumors larger than about 2 g. Despite the apparent increase in heat dissipation by the increased blood flow, the temperature of the skin was 42.6–42.8° C during the heating, possibly due to the direct contact of skin with the water at 43° C. The temperature of muscle was 41.1–41.8° C, and the temperature at the core of tumors larger than 2 cm in diameter was 42.3–42.7° C during the hyperthermia. The lower temperature in the muscle could be attributed to an increase in heat dissipation as a result of the increased blood flow. This differential rise in temperature by heating may account in part for the differential effect of hyperthermia on tumors and normal tissues in vivo.
Diseases of Children, Medical and Surgical.
Journal: JAMA (1907)

It is doubtful if it is wise to combine in so small a space, as in this instance, a discussion of both the medical and surgical diseases of children. The accumulation of knowledge has become too great, and the differentiation of labor has gone too far, to do this satisfactorily. One branch or the other will almost surely suffer. The pediatric side of this work has been well done and is pretty complete; the surgical side is not so complete. The general arrangement of subjects is logical and the one usually followed: physiology and diseases of the newly born, then the grouping of diseases according to systems, digestive, respiratory, etc. The section on diphtheria, however, would be more complete if laryngeal involvement were more thoroughly discussed here, rather than in the chapter on respiratory diseases. The section on hemorrhages of the newly born is not in accord with prevailing opinion.
Dissolution of Gallstones
Journal: JAMA (1972)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Ten Years of Operative Surgery in the Provinces
Authors: A. Prichard
Journal: BMJ (1860)

THE third subdivision will contain the operations upon the breast, all of which were on female subjects; and they are not very numerous.The diseases treated in this way were, hydatid tumour, cystosarcoma, the chronic mammary tumour, and carcinoma.to be the most common form, at any rate, in these tumours.CASE xciv.E. W., aged 44, with a tumour of the right breast of ten years growth.It had latterly increased more rapidly, and was about to ulcerate above the nipple, where it was adherent to the skin.The swellinds is of the size of her fist.Her general healthin Tood, and she is stout and well.I removed the tumour and adherent skin freely down to the pectoral muscle.Eight ligatures and four sutures were used, 893 =
A Tax Reform Strategy to Deal With the Uninsured
Authors: Stuart M. Butler
Journal: JAMA (1991)

The high level of uninsurance in the United States is due in large measure to the tax treatment of health care, which is based on the tax exclusion for company-provided plans. Correcting the perverse incentives for providers and patients resulting from this tax treatment is the crucial step to creating a national health care system that is affordable and efficient. The Heritage Foundation proposal calls for the elimination of the current tax exclusion and its replacement with a system of refundable tax credits for the purchase of health insurance and medical services. (<i>JAMA</i>. 1991;265:2541-2544)